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Due to the brain’s limited ischemic tolerance, even relatively brief episodes of inadequate delivery of oxygen (hypoxia) as well as impaired oxygenation and blood flow (hypoxia-ischemia) may result in the breakdown of structural integrity and impairment of brain function. The resultant brain damage may affect children during perioperative adverse events, such as hemodynamic instability and cardiopulmonary arrests, neurosurgical operations or open-heart procedures involving cardiopulmonary bypass. Long-term sequelae include neurobehavioral abnormalities, motor deficiencies, learning impairment and seizures. Exposing this dilemma, persisting developmental abnormalities have been documented in up to 50 percent of survivors of complex neonatal cardiac surgery. However, the exact threshold for inadequate oxygenation and / or blood flow to cause long-term impairment is not well known. Moreover, effective neuroprotective strategies during these periods of brain ischemia are lacking.
Anesthetics are frequently used in the perioperative setting. Their diverse mechanisms of action, which include interactions with sodium, potassium and calcium channels, acetylcholine, serotonin, g-aminobutyric acid, glycine and glutamate receptors, as well as signaling proteins, make them an interesting target as neuroprotectants. Neuroprotective properties of several anesthetics have been examined, but mostly in models of the adult brain. It remains controversial, however, whether anesthetics can confer protection during severe ischemic insults and whether neuroprotection can be sustained beyond the immediate post-ischemic period.
Significant differences exist between the adult and the immature brain regarding susceptibility and effects of brain ischemia, suggesting the possibility for a differential response to protective strategies. Accordingly, we are investigating the effects of anesthetics during brain ischemia on neuronal structure as well as long-term neurocognitive function in the immature brain. Moreover, we are examining the mechanisms underlying hypoxic-ischemic brain injury and are testing noninvasive monitoring strategies.
Previous results from our laboratory have demonstrated protective effects of the inhaled anesthetic Desflurane in models relevant to congenital heart surgery and hypothermic cardiopulmonary bypass. These findings have contributed to a shift from the high-dose narcotic anesthetic during infant heart surgery to a more balanced anesthetic, including inhaled anesthetics. Moreover, we are studying the long-term neurobehavioral effects of the volatile anesthetic Sevoflurane as a neuroprotectant.
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